CRISPR-Cas9 Used to Treat Patient with Beta Thalassemia

The Swiss healthcare startup CRISPR Therapeutics has used the CRISPR-Cas9 gene editing tool as a treatment for transfusion-dependent beta thalassemia in a clinical trial sponsored by Vertex Pharmaceuticals of Boston. This is the first time that CRISPR-Cas9 has been used in a company-sponsored clinical trial in the west. CRISPR-Cas9 has already been used to treat patients in China, where regulations on new treatments are less stringent.

Transfusion-dependent beta thalassemia (TDT) is a life-threatening genetic blood disorder. Patients with TDT have inherited a faulty copy of the gene responsible for producing hemoglobin or have a mutation in that gene. As a result, patients have reduced levels of hemoglobin which limits the ability to of the body to deliver oxygens to cells.

The condition causes weakness, fatigue, and there can be serious complications, including an increased risk of blood clots, cancer, and organ failure. Bone marrow transplants are an option for some patients, provided a suitable donor can be found. Patients also require regular blood transfusions and iron chelation therapy to treat iron overload from blood transfusions. Even with these treatments, patients can suffer serious complications from the disease and life expectancy is seriously reduced.

Enter CRISPR-Cas9. CRISPR-Cas9 is being used in the clinical trial to correct the genetic defect and, it is hoped, bring hemoglobin levels up to a normal level.

The first patient to receive this treatment has had bone marrow stem cells collected, altered in the lab using CRISPR-Cas9 to correct the default in the hemoglobin gene, and the altered cells have been reintroduced into the bloodstream. The patient is being monitored to determine whether the stem cells form healthy blood cells and if that is the case, how effective the treatment is over time.

The trial also involves a second use of CRISPR-Cas9. The faulty gene is not the only gene responsible for hemoglobin production. A second gene provides instructions for making fetal hemoglobin during development, but the gene is switched off around 6 months after birth. If the fetal hemoglobin gene can be switched back on, hemoglobin production in patients with TDT could be increased to near normal levels.

A second patient will now receive this form of CRISPR-Cas9 therapy to reactivate the fetal hemoglobin gene. After patients have been assessed and the treatment has been shown to be successful, further patients will be enrolled in the clinical trial. CRISPR Therapeutics is also planning on extending the trial to attempt to cure another serious inherited hemoglobinopathy: Sickle cell disease.

Both methods of treatment could potentially serve as a cure for beta thalassemia that could be provided as a one-time treatment, eliminating the need for blood transfusions.